Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification.

Etra A, Gergoudis S, Morales G, Spyrou N, Shah J, Kowalyk S, Ayuk F, Baez J, Chanswangphuwana C, Chen YB, Choe H, DeFilipp Z, Gandhi I, Hexner E, Hogan WJ, Holler E, Kapoor U, Kitko CL, Kraus S, Lin JY, Al Malki M, Merli P, Pawarode A, Pulsipher MA, Qayed M, Reshef R, Rösler W, Schechter T, Van Hyfte G, Weber D, Wölfl M, Young R, Özbek U, Ferrara JL, Levine JE (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Book Volume: 6

Pages Range: 3707-3715

Journal Issue: 12

DOI: 10.1182/bloodadvances.2022007296

Abstract

We used a rigorous PRoBE (prospective-specimen collection, retrospective-blinded-evaluation) study design to compare the ability of biomarkers of systemic inflammation and biomarkers of gastrointestinal (GI) tissue damage to predict response to corticosteroid treatment, the incidence of clinically severe disease, 6-month nonrelapse mortality (NRM), and overall survival in patients with acute graft-versus-host disease (GVHD). We prospectively collected serum samples of newly diagnosed GVHD patients (n = 730) from 19 centers, divided them into training (n = 352) and validation (n = 378) cohorts, and measured TNFR1, TIM3, IL6, ST2, and REG3α via enzyme-linked immunosorbent assay. Performances of the 4 strongest algorithms from the training cohort (TNFR1 + TIM3, TNFR1 + ST2, TNFR1 + REG3α, and ST2 + REG3α) were evaluated in the validation cohort. The algorithm that included only biomarkers of systemic inflammation (TNFR1 + TIM3) had a significantly smaller area under the curve (AUC; 0.57) than the AUCs of algorithms that contained ≥1 GI damage biomarker (TNFR1 + ST2, 0.70; TNFR1 + REG3α, 0.73; ST2 + REG3α, 0.79; all P < .001). All 4 algorithms were able to predict short-term outcomes such as response to systemic corticosteroids and severe GVHD, but the inclusion of a GI damage biomarker was needed to predict long-term outcomes such as 6-month NRM and survival. The algorithm that included 2 GI damage biomarkers was the most accurate of the 4 algorithms for all endpoints.

Authors with CRIS profile

Involved external institutions

Icahn School of Medicine at Mount Sinai United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Chulalongkorn University / จุฬาลงกรณ์มหาวิทยาลัย Thailand (TH) Massachusetts General Hospital United States (USA) (US) Ohio State University United States (USA) (US) Penn Medicine United States (USA) (US) Mayo Clinic United States (USA) (US) Universität Regensburg Germany (DE) Vanderbilt University United States (USA) (US) Universitätsklinikum Würzburg Germany (DE) City of Hope Medical Center United States (USA) (US) Ospedale Pediatrico Bambino Gesu Italy (IT) University of Michigan United States (USA) (US) Children's Hospital Los Angeles United States (USA) (US) Emory University United States (USA) (US) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) The Hospital for Sick Children (SickKids) Canada (CA) Julius-Maximilians-Universität Würzburg Germany (DE)

How to cite

APA:

Etra, A., Gergoudis, S., Morales, G., Spyrou, N., Shah, J., Kowalyk, S.,... Levine, J.E. (2022). Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification. Blood Advances, 6(12), 3707-3715. https://doi.org/10.1182/bloodadvances.2022007296

MLA:

Etra, Aaron, et al. "Assessment of systemic and gastrointestinal tissue damage biomarkers for GVHD risk stratification." Blood Advances 6.12 (2022): 3707-3715.

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